Air Pollution and Heart Health:Making the Connection

Washington, DCSeptember 28, 2016

Wayne Cascio, MD, FACC, FAHA

Director, Environmental Public Health Division

National Health and Environmental Effects Research Laboratory

Office of Research & Development, US EPA

Research Triangle Park and Chapel Hill, NC

Healthcare-EnvironmentalPublic Health Workshop

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• Why should communities care about ambient air pollutants?

• Why should healthcaresystems care about ambient air pollutants?

• Why should health care providers care aboutambient air pollutants?

• Why should their patients care about ambient air pollutants?

Ambient Air Pollution & Health

EPA and AHA State that PM

CAUSES Mortality and Morbidity

EPA:

“Epidemiologic evidence

is sufficient to conclude

that a causal relationship

exists between: short-

term and long-term

exposure to PM2.5 and

mortality.”

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Integrated Science Assessment(ISA) for Particulate Matter 2009

• “Air pollution should be viewed as one of several major modifiable risk factors in the prevention and management of cardiovascular disease.”

• “Health professionals, including cardiologists, have an important role to play in supporting educational and policy initiatives as well as counseling their patients.”

4Newby DE et al. Eur Heart J 2014

Call for Public Health &Healthcare Action

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

Air Pollution DeathsComparable to Alzheimer’s, Diabetes, Flu

5Cause of Death

National Vital Statistics Report 2016

0

10

20

30

% o

f Tota

l D

eath

s ~130,000 excess deaths attributedto outdoor air pollution in the U.S.

(No. of Deaths in Thousands)

740

585

85 76 57131149

384147 36

Estimated Excess MortalityBurden of Air Pollution Deaths by County

Fann et al. Risk Analysis 20126

PM2.5 and O3-related Mortality by County based on 2005 air pollution levels

US EPA’s BENMAPhttp://www.epa.gov/airquality/benmap/index.html

2,800 to 5,400

800 to 2,799380 to 799160 to 379

20 to 159< 19

6

7

PM Causes Both Short- and

Long-term Health Impacts

Coarse

PM10

PM2.5

Short-term clinical events- Associated with daily transient changes

(BLUE arrows)

Long-term clinical events- associated with annual average

(YELLOW line)

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Population

studies and

cardiovascular

health effects

of particle air

pollution

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Clinical cardiovascular endpoints from epidemiological studies at ambient concentrations

Brook et al. Circulation 2010

Epidemiological EvidencePM2.5-Related Air Pollution Effects

10Miller et al. NEJM 2007

PM2.5 Increases Risk in WomenFirst Cardiovascular Event or Death

AnnualNAAQS

PM2.5 = 12µg/m3

Hazard Ratio

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Air Pollution Triggers Heart AttacksLow PM exposure associated with lower risk

Population Attributable Fractions (PAF)Related to: the strength of the association between exposure to a risk factor and the prevalence of this risk factor within the population

Modified from Nawrot et al. Lancet 2011

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Air Particle Pollution and StrokeShort-term Exposure & Ischemic Stroke

Risk Ratio1.00 1.150.90 0.95 1.05 1.10

Hemorrhagic

Ischemic

Cerebrovascular

Across all outcomes

Shin HH, et al. Epidemiology 2014Wellenius G, et al. Arch Intern Med 2012

Within a population: low levels of PMare associated with ischemia stroke

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Does Air Pollution

Increase

Atherosclerosis?

14Kaufman JD et al. Lancet 2016

Long-Term PM2.5 & NO2 ExposureIncreases Coronary Artery Calcium

Long-term PM2.5 and NO2 increased coronary calcium,an indictor of atherosclerosis

PM2.5 (5µg/m3)

NOx (40ppb)

Black carbon(0.5µg/m3)

NOx (10ppb)

Air Pollutants

Agatston units per year Long-term average PM2.5 (µg/m3)

Aga

tsto

nu

nit

s p

er y

ear

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Possible

Mechanisms

16Brook et al. Circulation 2010

Exposure to PM2.5, Traffic- and Combustion Related Air Pollution

Hajat et al. Epidemiology 2015

MESA Air

Long-term exposure:5 µg/m3 PM2.5 associated with:• 6% higher IL-6

(95% CI = 2%, 9%)

40 ppb NOx associated• 7% higher level of D-dimer

(95% CI = 2%, 13%)

Short-term exposure:Daily PM2.5 level associated with:• CRP• Fibrinogen• E-selectin

Human Studies Show Increases in

Subclinical CV Endpoints

Pulmonary oxidative

stress & inflammation

Blood

Bronchioles/Alveoli

PM or constituents

in the circulationANS imbalance

PM

SNS / PSNSUFP, soluble metals

Organic compounds

Neural Response

SYSTEMIC

“SPILL-OVER”

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1

ANS

Circulating Constituents

CELLS: activated WBCs, platelets, myeloperoxidase, Plt-MΦ

CYTOKINES: IL-1β, IL-6, TNF-α

OTHER: ET, histamine, ? Microparticles, ox-LDL, dysFx HDL

Acute phase

response

Clotting factors

Fibrinogen, CRP

Adipokines(PAI-1, Resistin)

Activated or

Inflamed fat

Activated or

Inflamed liver

Systemic Oxidative stress and Inflammation

Direct actions

CARDIOVASCULAR INFLAMMATION + ROS/RNS

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ACUTE: Endothelial dysfunction, Vasoconstriction, Plaque instabilityCoagulation, Thrombosis, Arrhythmias

CHRONIC: LV hypertrophy, Atherosclerosis, Arterial StiffnessMetabolic Syndrome: HTN, Insulin resistance, Dyslipidemia

Reducing Air Pollution Decreases

Health Risk

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Harvard Six-Cities StudyPM Decreased, Mortality Decreased

Period 1 Period 21974-89 1990-98

Person Years 104,243 54,735On follow-up

Deaths 626 570City-specific modelPortage 1.00Topeka 1.03 1.00Watertown 1.19 0.82Harriman 1.33 1.23St. Louis 1.21 0.96Steubenville 1.48 1.21

Period 1.00 0.96

Laden et al. AJRCCM 2006

Cox Proportional Hazards Model

Adjusted CV Mortality Rate Ratios

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P - Portage, WI

T - Topeka, KS

W - Watertown, MA

L - St. Louis, MO

H - Harriman, TN

S - Steubenville, O

Bold - Period 1

Estimated adjusted rate ratios for total mortality and PM2.5

Laden et al. AJRCCM 2006

Harvard Six-Cities Study

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Harvard Six-Cities Study

P - Portage, WI

T - Topeka, KS

W - Watertown, MA

L - St. Louis, MO

H - Harriman, TN

S - Steubenville, OH

Bold - Period 1

Italics - Period 2

Estimated adjusted rate ratios for total mortality and PM2.5

Laden et al. AJRCCM 2006

Summary

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• Particle pollution increases short- and long-term cardiovascular morbidity and mortality

• Aged-adults, those with pre-existing heart disease, and diabetes are at higher risk

• Mechanisms are under investigation but are likelyrelated to effects on oxidative stress, autonomic control and inflammation

• Improvements in air pollution levels reduce health impacts and increase life expectancy

• Reductions of short-term exposures in those at higher risk are predicted to mitigated adverse health effects

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Questions?